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Immune system genes implicated in multiple sclerosis

Analysis of a study published in a science journal   |   By Dr Gurdeep Sagoo   |   Published 12 August 2011
Study: Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
By: Sawcer S. et al. (200 authors total)
In: Nature
Link: http://dx.doi.org/10.1038/nature10251
What this study set out to do:

This consortium of 23 research groups across 15 countries set out to identify novel susceptibility loci associated with multiple sclerosis (MS).

How they went about it:

The researchers conducted a genome-wide association study (GWAS) involving 9,772 MS patients and 17,376 controls of European descent with data on nearly 500,000 single nucleotide polymorphisms (SNPs). One hundred and two SNPs were taken forward for replication in 4,218 MS patients and 7,296 controls. Additional analyses were conducted to identify functional genes in close proximity to identified SNPs.

Outcome:

Twenty-three of 26 previously identified associations were replicated along with the identification of 29 novel associations. A third of these loci also overlapped with other autoimmune diseases and 30% of the genes identified near the SNPs of interest are involved in the immune system process. A further five suggestive associations only just failing to reach genome-wide significance were also identified. 

Conclusion:

This study reinforces the view that the GWAS design combined with a very large sample size can still provide valuable genetic insights into common complex diseases. Immunologically relevant genes are significantly overrepresented among the genes mapping close to the SNPs identified in this study and collectively highlight the importance of this biological process in disease pathogenesis.

Our view:

This large multi-national GWAS has doubled the number of known associated susceptibility loci to more than 50 with around a third of identified regions in this study overlapping with other autoimmune diseases and containing genes linked to the immune system. Also implicated were genes related to environmental risk factors such as Vitamin D (See previous news) and MS therapies such as natalizumab and daclizumab. Greater refinement of associations within the MHC, a region of the genome involved in the immune system that is notoriously difficult to work with because of extensive linkage disequilibrium, were also achieved with the identification of HLA-DRB1 risk alleles with variation in the HLA-A gene providing protective alleles. These findings strengthen the idea that MS is autoimmune in nature and has implicated many leads for researchers to follow–up with talk of treatment and prevention still premature.

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